The CON portion of the PRO/CON debate between Drs. Brian Olshansky and John Mandrola currently featured presents a conundrum within the fields of electrophysiology and geriatric cardiology.

Cardiovascular (CV) clinical trials often fail to enroll an adequate number of older adults. Furthermore, in the rare instances where clinical trials focus on recruiting older participants, there is a lack of representation of real-life older adults. Outside of trials, older adults with atrial fibrillation (AF) often have a substantial burden of physical, cognitive, financial, and social abnormalities.

This debate represents an attempt at exposing the different tensions in AF-treatment strategies in older patients. It involves the determination of not only CV factors but also intricate geriatric conditions and considers what matters most to the patient.

See the brief clinical vignette in this poll: Mr. PT is an 82-year-old man who presents with persistent, mildly symptomatic, AF of approximately 4-5 months duration. He also has heart failure with reduced ejection fraction (HFrEF), New York Heart Association (NYHA) Class 2 HF and a left ventricular (LV) ejection fraction of 40%.

Point 1: AF ablation in the best of circumstances has modest success rates.

The success rate from the seminal paper out of Bordeaux, France in 1998 was approximately 60%.¹ Similar success rates were demonstrated in the CABANA (Catheter ABlation vs ANtiarrhythmic Drug Therapy for Atrial Fibrillation)² trial, published 20 years later. The lack of progress is likely because the field of electrophysiology will need to better appreciate the pathophysiology of AF.

The CABANA trial of hard CV outcomes failed to show a benefit of AF ablation over antiarrhythmic drugs. Proponents of AF ablation could cite the positive CASTLE-AF (Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation)³ trial, which found a significant reduction in the primary endpoint of death or hospitalization for HF in patients with HF and AF. CASTLE AF, however, should be interpreted with caution. Trialists screened 3,000 patients to enroll approximately 300 patients and the study was underpowered due to early termination and a very small number of outcome events.

In addition to poor outcome data, AF ablation has yet to be shown effective in improving quality of life in a proper placebo (sham) controlled trial.

Point 2: The second argument against AF ablation in older adults turned on evidence translation.

The entire evidence base of AF ablation, albeit limited, as discussed above, stems from younger mostly male patients. Three major HF trials, CASTLE-AF, CASTLE HTx (Catheter Ablation in End-Stage Heart Failure With Atrial Fibrillation),⁴ and AATAC (Ablation vs. Amiodarone for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure and Implanted ICD/CRTD),⁵ each enrolled mostly men in their early sixties. Even if interpreted generously, it is unlikely these trials apply to elderly patients, especially older women.

Point 3:  Evidence translation to older adults is fraught.

The complexities of care in older adults with cardiovascular diseases are vast. Balancing the primary major adverse cardiovascular outcome, benefit from treatment, treatment harm and competing risks is a difficult task. Navigating these issues could be analogous to walking a tightrope.⁶ On the one side of treatment benefit is treatment harm. Clearly older adults are more apt to have complications from invasive procedures. The other effect on treatment benefit concerns the risk of the primary endpoint versus competing risks. An ideal patient and ideal treatment would include a patient who has the primary outcome as their main risk. A good example is implantable cardioverter-defibrillator (ICD) therapy. An ICD is most likely to confer net benefit when a patient has cardiac arrest as their main risk. When there are many competing risks, the likelihood of net benefit declines.

In an older patient with AF and HF, there are many competing risks of death or HF. AF ablation is only able to treat one of those risks.

Point 4: Excellent alternatives to primary AF ablation exist.

Findings from the APAF-CRT (AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS)⁷ trial need to be considered. The APAF-CRT trial studied atrioventricular node ablation plus cardiac resynchronization therapy (CRT) versus medical therapy in patients with AF and HF. This trial found a substantial reduction in mortality and HF events in the ablation and CRT arm. Yet now CRT can be accomplished with single lead conduction system pacing. This is an under-used highly beneficial therapy.

References

1. Haïssaguerre M, Jaïs P, Shah DC, et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-66.
2. Chew DS, Li Y, Cowper PA, et al., on behalf of the CABANA Investigators. Cost-effectiveness of catheter ablation versus antiarrhythmic drug therapy in atrial fibrillation: the CABANA randomized clinical trial. Circulation 2022;Jun 21:[Epub ahead of print].
3. Marrouche NF, Brachmann J, Andresen D, et al., on behalf of the CASTLE-AF Investigators. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med 2018;Feb 1:[Epub ahead of print].
4. Sohns C, Fox H, Marrouche NF, et al., on behalf of the CASTLE HTx Investigators. Catheter ablation in end-stage heart failure with atrial fibrillation. N Engl J Med 2023;389:1380-89.
5. Di Biase L, Mohanty P, Mohanty S, et al. Ablation versus amiodarone for treatment of persistent atrial fibrillation in patients with congestive heart failure and an implanted device: results from the AATAC multicenter randomized trial. Circulation 2016;133:1637-44.
6. Foy AJ, Schaefer EW, Ruzieh M, et al. Re-analyses of 8 historical trials in cardiovascular medicine assessing multimorbidity burden and its association with treatment response. Am J Med 2024;Feb 6:[ePub ahead of print].
7. Brignole M, Pentimalli F, Palmisano P, et al; APAF-CRT Trial Investigators. AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: the APAF-CRT mortality trial. Eur Heart J 2021;42:4731-39.